Hyperinsulinism has been postulated as a possible stimulus to somatomedin (SM) synthesis by the perfused rat liver and in man. Seven children who presented with severe fasting hypoglycemia and who had documented hyperinsulinism were studied to explore the effect of excessive endogenous insulin secretion on plasma levels of the SMs. Neither the concentration of somatomedin C/insulin-like growth factor-I (SMC/IGF-I) (mean +/- SD, 0.53 +/- 0.37 U/ml) nor that of IGF-II (1.10 +/- 0.58 microgram/ml) was significantly different from values observed in normal children. SMC/IGF-I and IGF-II were inversely correlated. There was a positive correlation between SMC/IGF-I and body weight, and an inverse correlation among IGF-II, body weight, and length. These results suggest that in children with normal GH secretion, hyperinsulinism sufficient to cause severe recurrent hypoglycemia does not result in an increase in either SMC/IGF-I or IGF-II concentrations in plasma.